109 research outputs found
DS1_JVDI_10.1177_1040638719828412 – Supplemental material for Effect of temperature and time on the thanatomicrobiome of the cecum, ileum, kidney, and lung of domestic rabbits
No full textSupplemental material, DS1_JVDI_10.1177_1040638719828412 for Effect of temperature and time on the thanatomicrobiome of the cecum, ileum, kidney, and lung of domestic rabbits by Kelsey E. Lawrence, Khiem C. Lam, Andrey Morgun, Natalia Shulzhenko and Christiane V. Löhr in Journal of Veterinary Diagnostic Investigation</p
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Development and implementation of a transkingdom network analysis pipeline to identify drivers of disease
No full textThe gut microbiome has been previously implemented in a number of diseases. Of note is its substantial role in metabolic syndrome, which encapsulates a group of conditions that increase the risk of cardiovascular disease, type 2 diabetes, and stroke. Understanding the causal relationships between the gut microbiome and host processes that influence disease has proved challenging, as the availability of easy-to-use software that does not require large sample sizes is lacking. As such, my work has aimed to develop a software pipeline called transkingdom network analysis (TkNA) that models biological systems from multi-omic data, using a top-down network biology approach. I then sought to utilize TkNA on real-world data to identify microbiota responsible for the anti-inflammatory effects of tetrahydroxanthohumol (TXN), which were previously identified in mice. Mice in the TXN study were raised on either a low-fat diet or a high-fat diet, with or without TXN treatment, and the TkNA pipeline was used to analyze the resulting microbial, transcriptomic, metabolic, and phenotypic outcomes. As a result, I was able to identify the adipose tissue as one of the key tissues affected by TXN treatment, specifically myeloid cells that are responsible for inflammatory responses. In addition, I showed TXN improved levels of many microbes. Specifically, the network reconstruction and interrogation capabilities of TkNA were used to identify a microbe belonging to the Oscillibacter genus that played a causal role in the development of high fat diet induced metabolic disease. This work was then experimentally validated in vitro using macrophage cell lines. This new software using existing analytical ideas and principles of causality, combined with the evidence that it can find causal factors in disease, lays the foundation for future work to study additional diseases
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Unexpected links reflect the noise in networks
No full textGene regulatory networks are commonly used for modeling biological processes and revealing underlying molecular mechanisms. The reconstruction of gene regulatory networks from observational data is a challenging task, especially considering the large number of players (e.g. genes) involved and the small number of biological replicates available for analysis. Herein, we propose a new statistical method for estimating the number of erroneous edges in reconstructed networks that strongly enhances commonly used inference approaches. This method is based on a special relationship between correlation and causality, and allows for the identification and to removal of approximately half of all erroneous edges. Using the mathematical model of Bayesian networks and positive correlation inequalities we establish a mathematical foundation for our method. Analyzing existing biological datasets, we find a strong correlation between the results of our method and the commonly used false discovery rate (FDR) technique. Furthermore, simulation analysis demonstrates that with large networks our new method provides a more accurate estimate of network error than FDR
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Identification of Cervical Cancer Key Regulators using Network Biology Approach - Supplementary tables
No full textThis data contains large supplementary tables for the PhD dissertation of Dariia Vyshenska. Title of the Dissertation: "Identification of Cervical Cancer Key Regulators using Network Biology Approach"
The dataset contains data from two types of research.
Research #1: Identification of bacterial regulators of cervical cancer gene expression. It contains microbial community’s data from cervical cancer samples of human patients. Prevotella bivia was identified as a key bacterial regulator of cervical cancer gene expression using reconstruction of transkingdom network from patient’s gene expression and bacterial abundance data. The data contains transkingdom network, information about bacteria found in each sample of cervical cancer, qRT PCR primers that were used to test host genes for being regulated by P. bivia.
Research #2: Identification of key cervical cancer driver genes and their combinations that are critical for cancer proliferation. We identified 9 host genes responsible for cancer cell growth and identified the pairs of these driver genes that have the highest impact on the cancer proliferation. To achieve this goal, we identified targets of each driver gene and reconstructed gene co-expression network out of the union of these targets. The data contains gene co-expression network, qRT PCR primers for 34 tested potential drivers, network measurements for each confirmed driver gene (average shortest path, number of proliferation associated targets), and proliferation measurements for single driver or driver pairs knock downs
Molecular mechanisms of proteins - targets for SARS-CoV-2 (review)
No full textThe rapidly accumulating information about the new coronavirus infection and the ambiguous results obtained by various authors necessitate further research aiming at prevention and treatment of this disease. At the moment, there is convincing evidence that the pathogen affects not only the respiratory but also the central nervous system (CNS). The aim of the study is to provide an insight into the molecular mechanisms underlying the damage to the CNS caused by the new coronavirus SARS-CoV-2. Results. By analyzing the literature, we provide evidence that the brain is targeted by this virus. SARS-CoV-2 enters the body with the help of the target proteins: angiotensin-converting enzyme 2 (ACE2) and associated serine protease TMPRSS2 of the nasal epithelium. Brain damage develops before the onset of pulmonary symptoms. The virus spreads through the brain tissue into the piriform cortex, basal ganglia, midbrain, and hypothalamus. Later, the substantia nigra of the midbrain, amygdala, hippocampus, and cerebellum become affected. Massive death of neurons, astrogliosis and activation of microglia develop at the next stage of the disease. By day 4, an excessive production of proinflammatory cytokines in the brain, local neuroinflammation, breakdown of the blood-brain barrier, and impaired neuroplasticity are detected. These changes imply the involvement of a vascular component driven by excessive activity of matrix metalloproteinases, mediated by CD147. The main players in the pathogenesis of COVID-19 in the brain are products of angiotensin II (AT II) metabolism, largely angiotensin 1-7 (AT 1-7) and angiotensin IV (AT IV). There are conflicting data regarding their role in damage to the CNS in various diseases, including the coronavirus infection. The second participant in the pathogenesis of brain damage in COVID-19 is CD147 - the inducer of extracellular matrix metalloproteinases. This molecule is expressed on the endothelial cells of cerebral microvessels, as well as on leukocytes present in the brain during neuroinflammation. The CD147 molecule plays a significant role in maintaining the structural and functional integrity of the blood-brain barrier by controlling the basal membrane permeability and by mediating the astrocyte-endothelial interactions. Via the above mechanisms, an exposure to SARS-CoV-2 leads to direct damage to the neurovascular unit of the brain
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Exploring the Gut Microbiome of Captive Elephas maximus Experiencing Abnormal Feces
No full textThe gut microbiome of all mammals is composed of a diverse commune of microorganisms including bacteria, fungi, archaea, protozoa and viruses 1. Studies have shown a symbiotic relationship between the gut microbiome and host physiology, with there being implications in health and disease progression 2. In captive animals, there has been evidence that has identified possible associations with living conditions or other anthropogenic effects and alterations in the gut microbiome of those animals. Although not shown in previous studies, it could be possible that these changes in the diversity of the gut microbiome may have implications in gastrointestinal diseases such as colitis or the appearance of abnormal fecal matter. This study aims to explore the gut microbiome of five elephants at the Oregon Zoo who faced alterations in normal stool production, characterized by the presence of mucus or a deviation in the consistency of the stool. This thesis aims to provide a preliminary exploration into the gut microbiome of these elephants to understand the differences in abundance of certain bacteria and identify targets for further comparisons and metagenomic analysis. Fecal samples from elephants were processed for DNA and PCR products were then sequenced. Sequencing data was processed and analyzed using DADA2 and MicrobiomeAnalyst to develop plots depicting alpha and beta diversity. It was found that relative to healthy controls from other zoos, the Oregon elephants had significant differences in beta diversity, signifying that there may be changes to the abundances of bacteria in their gut microbiome. Presence of certain phyla such as Firmicutes and Bacteroides were found in the fecal samples, which was supported by previous literature that indicated these bacteria to be dominant in elephants found in captivity. No significant difference was found in beta diversity between elephants experiencing normal stool versus loose stool and elephants experiencing presence in mucus versus absence in mucus, which prompts further investigations. The eventual results provided from this thesis may be beneficial in identifying potential samples or elephants which can be used in further comparisons to identify specific bacteria that may have implication in the abnormal stool appearance. We hope that recognizing differences in gut microbiome between elephants experiencing chronic abnormal feces and normal feces may provide specific pathogenic targets for treatment. If there are significant bacterial targets, changes in treatment can be considered by veterinarians using available medications, hopefully providing more efficient care.Keywords: microbiome, gut, elephants, feces, diversit
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Determination of the relationships between functional genomic content and phenotypic effects of probiotic supplementation on metabolic disease: the first steps toward an efficient pipeline for annotation and analysis
No full textProbiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit to the host”. A wide variety of putative probiotics exist on the market; however, clinical evidence of their efficacy is lacking. Probiotics have been previously used in the treatment of metabolic diseases like type 2 diabetes and obesity. This study aims to delineate conserved genomic regions of probiotic bacteria that are responsible for the improvements in disease outcome when supplemented to treat hosts with metabolic disease. This thesis will focus on a section of this aim, wherein the functional genomic regions of probiotic bacteria that are enriched when compared to the functional content of the average human gut microbiome will be determined. A systematic literature review was performed to identify probiotic bacterial strains used to treat metabolic disease. Following functional annotation of their genomes using the Clusters of Orthologous Genes (COG) database and enrichment analysis of probiotic Gene Ontology (GO), it was found that some genera of bacteria are enriched in GO terms that benefit host health when compared to the content of the average human microbiome. Also, functional annotation via the COG method provides insights into which genera contain more proteins relating to carbohydrate metabolism, lipid metabolism, and energy production and conversion. More analysis is required, but from the eventual results, we hope to better understand possible genetic drivers behind how specific bacteria function to improve the health of individuals with metabolic disease.Keywords: probiotics, probiotic supplementation, metabolic disease, Clusters of Orthologous Genes, Gene Ontolog
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Metagenomics Analysis Reveal Host-Microbe Interactions in Cervical Cancer
No full textCervical cancer is the fourth most common cancer in women worldwide. Recently it has been shown that microbiota play a role in some types of cancer. Therefore, to understand whether microbes contribute in any way to the development and progress of cervical cancer, we investigated the cervical microbiome via analysis of 16S rRNA sequencing data. Using qPCR we detected bacterial DNA in 121 out of 123 samples of cervical carcinoma. However, 16S library preparation and sequencing was possible for only the 58 samples with higher amounts of bacterial DNA. After matching our results with the Human Microbiome Project, principle coordinate analysis showed that the closest neighbors to cancer samples were healthy vaginal samples, representing compositional similarity. Overall, the alpha diversity of cervical cancer communities was quite high (Shannon index 3.88) compared to the healthy microbiome of other body sites. Furthermore, the most abundant genera in these samples were Prevotella (17.0%), Fusobacterium (9.4%), and Porphyromonas (7.4%), all Gram-negative, anaerobic bacteria known to be associated with bacterial vaginosis. To explore host-microbe interactions, we reconstructed a transkingdom network between tumor gene expression and microbial relative abundances. Prevotella spp. was revealed as a key node with high bipartite betweenness centrality, and was found to induce the expression of key cancer driver genes in vitro. This study represents the first comprehensive integrative analysis of the microbiome and transcriptome in cervical cancer, showing the potential role of key bacteria in driving carcinogenesis
Refugees in the World: 2002. Achievements and Problems (Ilija Todorovic, Yury Morgun, Andrey Selivanov)
No full textРаздел "Международные отношения"This is a summary of the changes in the refugee situation in the world in 2002 and of the activities of the UNHCR.
The greatest progress for refugees has been achieved in Afghanistan: about 2 million refugees who had been forced out of the country, came back. Changes for the better took place in Sri Lanka where the conflicting sides stopped the ten-year-old long civil war and concluded a Norway-mediated agreement. And some of the first of a million refugees started returning home from exile. A hope for the end of an over 25-year-long civil war in Angola has emerged. A cease-fire has been reached and refugees are coming back. After the ten-year-long bloodshed the situation in Sierra-Leone started to come back to normal, with over 200 000 refugees having returned to the country. The main tasks in protecting refugees in the Balkans have been implemented, that is why the UNHCR is reducing its activities in the region, though some issues remain. East Timor has achieved full independence and 250 000 people returned home, with the conditions in the country coming back to normal so much that the UNHCR applied the 1951 Refugee Convention article on terminating its force.
Similarly, this article has been applied in regard to the refugees from Eritrea who had found temporary asylum in Sudan.
The refugee situation in Belarus is summed up. The main task of the UNHCRhere is assisting Belarusian authorities in humane management of disordered refugee flows with a focus to protecting the rights of asylum seekers and refugees according to international standards and norms.
A brief review is given to the unsolved issues such as the long-standing refugee crises and acute crisis refugee situations in various regions of the world: Liberia, Cote d'lvdire, Burundi, Sierra Leone, West Sahara, Colombia, Azerbaijan, Butan. The article concludes in a brief analysis of the prospects of further activity on reducing the acuteness of refugee crises: holding a global meeting of the representatives of 127 states on the problems of refugees in Geneva in 2001; adoption of the Protection Agenda, certain guidelines for governments and humanitarian organizations for their efforts in raising the refugee assistance efficiency; introducing new ideas by the High Commissioner of the UNHCR: the new approach to raise the effectiveness of the 1951 Convention, called Convention Plus; the appeal to join the efforts of some UN bodies to solve the problems of both refugees and local population, the new approach 4R, that is the idea of developing a holistic concept of refugee protection embracing four main stages: repatriation, reintegration, rehabilitation and reconstruction. "The results achieved in Afghanistan in 2002 were striking. We are facing further difficult tasks " (Ruud Lubbers)
The Refugee Problem Settlement in the Early 21st Century (Ilija Todorović, Yuri Morgun, Andrey Selivanov)
No full textРаздел "Международные отношения"The article presents an analysis of the refugee problem in the world and across the regions as well as the analysis of the most acute crises as of the beginning of 2004.
Due to the activity of the UNHCR, of various states and a number of international organisations the solution of the refugee problem in the beginning of the 21st century appears to be effective, with the refugee number reducing by over 3 million people. This is the greatest annual reduction over the last decades. At the same time, there are over 17 million refugees remaining in the world, so further intense work is required to alleviate the problem, primarily to settle protracted refugee crises. The situation remains unstable in a number of countries, which can lead to the emergence of new refugees. The article outlines the strategic goals of the UNHCR which are necessary to achieve for the refugee problem solution
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